An electrochemical label-free DNA impedimetric sensor with AuNP-modified glass fiber/carbonaceous electrode for the detection of HIV-1 DNA

ABSTRACT

Since coronavirus disease 2019 (COVID-19) outbreak, neurologic manifestations have been increasingly reported including encephalopathy;however, the underlying patho-physiology remains mostly unclear [1]. Neurotropism of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) has been suspected [2], though neuropathological studies did not show specific brain changes [3]. Besides the SARS-CoV-2 infection, a dysregulated immune response resulting in a massive release of proin-flammatory cytokines is involved in pathogenesis of severe COVID-19 manifestations and multi-organ failure [4]. This systemic hyperinflammatory state may be involved in neu-rologic impairment, as well. We report a case of COVID-19-related encephalopathy, questioning temporal relations between infection, cytokine storm, and neurologic involvement. A 77-year-old female, with no history of neurological disease , presented with impaired consciousness after 18-days history of SARS-CoV-2 infection and acute respiratory distress requiring invasive mechanical ventilation (Fig. 1). Patient was placed on hydroxychloroquine, levofloxacin, and piperacillin/tazobactam. Despite a remarkable respiratory improvement, at time of first neurologic evaluation, patient presented awake but mutacic, without any goal-directed behavior. No meningeal irritations or focal signs were found. Stimulus-induced myo-clonus and positive primitive reflexes (blinking, left grasp) were observed. Electroencephalogram (EEG) recording showed a generalized slowing activity, prevalent in frontal regions. A magnetic resonance imaging (MRI) displayed diffuse white-matter lesions consistent with chronic small vessel disease without contrast enhancement (Fig. 2). Cerebrospinal fluid (CSF) analysis detected normal white blood cell counts and mild increase of the blood-brain barrier permeability (CSF protein = 56 mg/dl, reference range < 50;CSF/serum albumin ratio = 15,6, reference range < 7,4). CSF reverse transcription-PCR (RT-PCR) for SARS-CoV-2 was negative. Additional CSF studies, including oli-goclonal bands, neurotropic virus, bacterial cultures, and autoimmune encephalitis antibody panel, were all negative. Cytokines levels were tested both in CSF and blood documenting a significant increase of interleukin-6 (IL-6) (55.1 and 9.1 pg/ml respectively, reference range < 5,9) and inter-leukin-8 (IL-8) (106 and 2721 pg/ml, respectively, reference range < 70) (Fig. 1). 18 F-fluorodeoxyglucose-positron emission tomography (18 F-FDG-PET/CT) scan showed a spread frontal lobe hypo-metabolism (Fig. 2). She was treated with intravenous methylprednisolone 60 mg for 10 days.